Abstract
Wear particle-stimulated inflammatory bone destruction and the consequent aseptic loosening remain major postoperative problems for artificial joints. Studies have indicated that puerarin promotes osteogenesis and alleviates lipopolysaccharide-induced osteoclastogenesis in vitro. However, the underlying molecular mechanism by which puerarin interacts with receptor activator of nuclear factor kappa-B ligand (RANKL)-mediated osteoclast formation in vitro and wear particle-stimulated osteolysis in vivo has not been reported. In this work, the protective effects exerted by puerarin on titanium particle-stimulated bone destruction in vivo and on RANKL-induced osteoclast activation in osteoclastic precursor cells in vitro were investigated. As expected, puerarin significantly inhibited wear particle-mediated bone resorption and proinflammatory cytokine productions in a calvarial resorption model. Additionally, puerarin inhibited RANKL-induced osteoclast activation, bone resorption ability, and F-actin ring formation in vitro as puerarin concentration increased. Furthermore, mechanistic investigation indicated that reduced RANKL-stimulated MEK/ERK/NFATc1 signaling cascades might regulate the protective effect of puerarin. Conclusively, these results indicate that puerarin, a type of polyphenol, might serve as a protective agent to prevent osteoclast-related osteolytic diseases.
Highlights
Artificial joint replacement has achieved great success in orthopedics and is considered the most effective surgical treatment for various end-stage hip and knee diseases (Goodman et al, 2014)
In the puerarin treatment groups, the severity of osteolysis and bone resorption was significantly alleviated by puerarin treatment
The major postoperative complication for artificial joints is aseptic loosening, which is mainly induced by wear debris from artificial implants (Holt et al, 2007; Rao et al, 2012)
Summary
Artificial joint replacement has achieved great success in orthopedics and is considered the most effective surgical treatment for various end-stage hip and knee diseases (Goodman et al, 2014). Wear debris, generated from the surface of implant materials, are responsible for the activation of the immune system and inflammatory reactions, which subsequently promote the secretion of proinflammatory cytokines (Rao et al, 2012; Gallo et al, 2013; Yang et al, 2016). These inflammatory cytokines can enhance osteoclast recruitment and function, interrupting the balance between osteogenesis and osteoclastogenesis (Murata et al, 2017; Ping et al, 2017b). An agent that inhibits inflammatory cytokines releases and the activation of osteoclastic function is a candidate for the protection and prevention of pathological osteolytic diseases.
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